The long-term objective of this research project is the development of a laser desorption electrospray ionization (LDESI) mass spectrometer source. The desorption laser is a tunable mid-IR laser system based on optical parametric oscillator (OPO) technology. The source will be available in front and back-side laser illumination modes depending on the application and have the option of UV laser light for matrix-assisted samples. To our knowledge, no commercially available source is available using both laser desorption and electrospray ionization. We envision a mass analysis of a variety of samples at room temperature and atmospheric pressure. Therefore, the sample would remain in its native environment and real time mass identification of sample constituents would be obtained with little to no sample pretreatment. Mass spectrometers using this technique will offer a useful tool to obtain mass identification for a variety of compounds important to fields such as proteomics, medical diagnostics, consumer products, pharmaceutical research and forensics. In an LDESI analysis, the sample is desorbed with the laser and the resultant plume of predominately neutral particles are captured and ionized by an electrospray source directed towards the mass spectrometer inlet millimeters above the sample surface. The key principle here is that desorption is separated from ionization. Analyzing samples in this way has many advantages over techniques that desorb and ionize in one step. One advantage is an increase in sensitivity since a larger portion of laser desorbed neutral particles are ionized by the electrospray. Also, high mass molecules in excess of 100 kDa can be analyzed at atmospheric pressure because of the "soft" mid-IR desorption and the multiple charging effect of ESI. We envision two types of laser desorption geometries in one source: front-side illumination for direct analysis of high mass proteins, gel separated proteins and bulk materials such as drug tablets and food products and back-side illumination for high spatial resolution tissue imaging and laser capture microdissection. Switching between the two sampling modes will simply involve changing fiber delivery position. When not using laser desorption, the electrospray remains in place for ESI MS. No switching of the LDESI source for the original electrospray source is necessary. The source will be constructed by OPOTEK, based on our past research with mid-IR OPO tunable lasers and MALDI MS sources. MS performance tests will be carried out on commercial mass spectrometers at the UCLA Department of Chemistry and Biochemistry through collaboration with Dr. Joseph Loo, an expert in the field of bioanalytical methods for the structural characterization of proteins. PUBLIC HEALTH RELEVANCE: The analytical device proposed in this grant application will provide a simple tool for researchers to analyze one of the most important groups of molecules necessary for the functioning of all living organisms: proteins. Learning about the characteristics of proteins will give our scientists the knowledge to develop better medical and forensic tools, medicines, food products, and other important fields relevant to the health and well-being of the general public. The proposed device will add capabilities to an existing analytical methodology called mass spectrometry where information about the structure of proteins can be obtained.